Efficacy and safety of 0.3% carbomer gel compared to placebo in patients with moderate-to-severe dry eye syndrome.

PURPOSE: Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed. METHODS: A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication. RESULTS: All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication. CONCLUSIONS: Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.

Corneal organ culture: effects of serum and a stabilised form of L-glutamine.

AIMS: Organ culture medium for corneas contains labile components, such as L-glutamine, whose loss could be a limiting factor to the length of storage. The medium is also supplemented with fetal bovine serum (FBS), which can vary significantly between different batches. The aim of this study was to establish the need for FBS during corneal organ culture, and to determine whether substitution of L-glutamine by the stable dipeptide L-analyl-L-glutamine was beneficial. METHODS: Porcine corneoscleral discs were suspended in 80 ml of organ culture medium (HEPES buffered Eagle's MEM with Earle's salts, 26 mmol/l NaHCO3, penicillin, streptomycin, and amphotericin B) and kept at 34 degrees C. The medium contained either 2 mmol/l L-glutamine or 2 mmol/l L-analyl-L-glutamine, and was either serum free or contained 2% FBS. At weekly intervals, five corneas from each group were stained with trypan blue and alizarin red S, and the surface area and shape of 100 endothelial cells were determined for each cornea. RESULTS: No differences were observed between corneas in organ culture medium with L-glutamine or L-analyl-L-glutamine. In serum free medium, endothelial cell density remained constant for the first week, but then declined rapidly over the next 2 weeks. With 2% FBS, there was no loss of endothelial cells for the first 2 weeks, but cell density had halved by the fourth week of organ culture. CONCLUSION: The presence of 2% FBS extended the period of endothelial stability, but no advantage was gained from the stabilised form of L-glutamine. The overall loss of endothelial cells was much greater than would be expected for human corneas.

Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.

AIMS: This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. METHODS: Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3% topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. RESULTS: Intracorneal concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ significantly (p = 0.33). CONCLUSIONS: Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin.

Group comparative trial of 2% nedocromil sodium with placebo in the treatment of seasonal allergic conjunctivitis.

A double blind group comparative trial comparing 2% nedocromil sodium with placebo in treating seasonal allergic conjunctivitis over a four week period is reported. Sixty-four patients were analysed. During the period of peak pollen challenge, statistically significant differences in favour of nedocromil sodium for itching and soreness were demonstrated. During a longer period of a less high pollen count, a significant difference in favour of nedocromil sodium was shown only for the symptom of soreness.

Topical ciprofloxacin in the treatment of blepharitis and blepharoconjunctivitis.

An international multicentre study assessed the clinical and antibacterial efficacy of a new topical ophthalmic formulation of the quinolone antimicrobial agent ciprofloxacin and compared it with that of tobramycin ophthalmic solution in patients with blepharitis and blepharoconjunctivitis. The study consisted of a randomised double-masked between-group evaluation of 464 patients, 230 of whom were treated with ciprofloxacin and 234 with tobramycin. There was qualitative and quantitative bacteriology, and clinical assessment of ocular symptoms and signs before and after a seven-day course of treatment. Bacteriological cultures demonstrated eradication or reduction of potentially pathogenic bacteria in 93.7% of eyes (ciprofloxacin) versus 88.9% of eyes (tobramycin), seven days after starting treatment. Clinically more than 80% of patients in both treatment groups were cured or improved after seven days. No statistically significant differences were observed between the two treatment groups. No serious side-effects were observed after use of either antimicrobial agent. Ciprofloxacin ophthalmic solution appears safe and effective. The spectrum of activity and clinical efficacy of this new formulation are discussed in comparison with currently used antimicrobial agents.

Evaluation of efficacy and safety of ciprofloxacin ophthalmic solution versus chloramphenicol.

The results of this clinical study demonstrate that ciprofloxacin ophthalmic solution 0.3% is as safe and as effective as 0.5% chloramphenicol ophthalmic solution in the treatment of conjunctivitis and blepharitis of bacterial aetiology. Both agents achieved microbiological improvement rates in excess of 90% after 1 week's treatment. On ciprofloxacin 93.5% of patients were judged clinically cured or improved versus 84.6% on chloramphenicol after 1 week. There were no serious adverse affects. One patient in each group suffered drug-related side-effects (chemosis, erythema) which resolved on discontinuation or changing of therapy. Cirpofloxacin is not associated with the rare, but serious, side effect of aplastic anaemia which is associated with chloramphenicol use. On the evidence of this study ciprofloxacin would appear to be an appropriate agent for general use as a topical ophthalmic formulation.

Antiviral drug sensitivity in ocular herpes simplex virus infection.

Thirty-nine herpes simplex virus (HSV) isolates were assayed for their sensitivity to 10 different antiviral agents. Of these 39 HSV isolates 10 were cultured from recipient buttons obtained at penetrating keratoplasty in patients with inactive stromal scarring due to recurrent herpetic keratitis, 25 were cultured from patients with conjunctival and ulcerative ocular infections, and the remaining four were laboratory strains with known drug sensitivity patterns, thus providing controls for the experiment. All but one of the 35 clinical isolates of HSV were type 1 and all were sensitive to the 10 antiviral agents. A single type 2 isolate from a young man with recurrent conjunctivitis proved to be resistant to a number of the antiviral agents. Since many of the clinical isolates had been exposed to multiple and protracted antiviral drug treatment, it is suggested that antiviral drug resistance in type 1 HSV ocular infection is not a significant problem.

A placebo-controlled blind trial of cyclosporin-A in prevention of corneal graft rejection in rabbits.

Cyclosporin-A (CyA) administered to rabbits intramuscularly in a dose of 25 mg/kg/day for 14 days following interlamellar corneal grafting had a significant effect in preventing rejection of the corneal graft (p less than 0.05), and the benefit was maintained. Rejection was attended by an initial mild inflammatory reaction and followed by a protracted intense response involving a variety of cell types, with subsequent loss of epithelium. endothelium and keratocytes, and the development of areas of stromal necrosis. CyA suppressed this rejection response.